Analyte database established using analyte data from non-invasive analyte sensors

ABSTRACT

Establishing an analyte database using analyte data that has been obtained using non-invasive analyte sensors, and using the analyte database to analyze data obtained using a non-invasive analyte sensor. Once the analyte database is established, the analyte database can be updated with new analyte data, and the analyte database can be used to analyze the new analyte data to derive information from the new analyte data. For example, in the case of a human target, the new analyte data together with the analyte database can be used to predict an actual or possible abnormal medical pathology of the human target.

FIELD

This technical disclosure relates to apparatus, systems and methods ofestablishing an analyte database using analyte data that has beenobtained using one or more non-invasive analyte sensors, and using theanalyte database to analyze data obtained using a non-invasive analytesensor.

BACKGROUND

A sensor that uses radio or microwave frequency bands of theelectromagnetic spectrum for non-invasive collection of analyte data ofa subject is disclosed in U.S. Pat. No. 10,548,503. Additional examplesof sensors that purport to be able to use radio or microwave frequencybands of the electromagnetic spectrum to detect an analyte in a personare disclosed in U.S. Patent Application Publication 2019/0008422 andU.S. Patent Application Publication 2020/0187791.

SUMMARY

This disclosure relates generally to establishing an analyte databaseusing analyte data that has been obtained using non-invasive analytesensor(s), and using the analyte database to analyze data obtained usinga non-invasive analyte sensor. Once the analyte database is established,the analyte database can be updated with new analyte data, and theanalyte database can be used to analyze the new analyte data to deriveinformation from the new analyte data.

The analyte data used to establish the analyte database is obtained overa period of time from a plurality of human or animal subjects (orcollectively subjects), from a plurality of animate or inanimatematerials, or from a plurality of other objects. The human or animalsubjects, the animate or inanimate materials, and any other objects fromwhich analyte data is obtained using the non-invasive analyte sensorsmay collectively be referred to as targets. The targets used toestablish the analyte database are similar to one another. For example,the targets can be humans; the targets can be the same kind of animalsuch as cows (or breed of cows); the targets can be the same kind oftrees (such as apple trees) or the same kind of fluid such as fuel, oil,hydraulic fluid, edible or potable liquids, or the like.

In another embodiment, analyte data used to establish the analytedatabase is obtained over a period of time from a single target so thatthe analyte database is specific to a single target. Additional analytedata can then be obtained from the target, the analyte database updatedwith the additional analyte data.

The term “analyte” used herein refers to a substance whose constituentsare being identified and/or measured. For example, glucose is a sugarthat is a component of many carbohydrates. The analyte is present in ahost which can be a liquid, gas, solid, gel, and combinations thereof.

The analyte data stored in the analyte database may be raw, unprocesseddata that is obtained by the analyte sensor. The raw, unprocessed datamay then be analyzed to extract out data on the analyte such as thepresence of the analyte and/or a concentration of the analyte. Theanalyte data stored in the analyte database may alternatively beprocessed data regarding the analyte such as the presence of the analyteand/or a concentration of the analyte. The analyte data stored in thedatabase may also be a combination of raw, unprocessed data andprocessed data. Regardless of the form of the analyte data stored in theanalyte database, the analyte data contains information on at least oneanalyte in the targets. In an example where the targets are human oranimal subjects, the analyte may be an indicator of an abnormal (ornormal) medical pathology of the subjects. In an example where thetargets are animate or inanimate materials, the analyte may be anindicator of an abnormal (or normal) condition of the materials such as,but not limited to, a contaminant or other impurity in the materials, adisease condition of the materials, a mineral in soil, and many others.

The analyte data used to establish the analyte database is collectedover a period of time that is sufficient to eliminate or minimize theeffects of temporary variations or aberrations in the analyte of thetargets. This helps to ensure that an accurate actual or possibleabnormal (or normal) indicator in the subsequently obtained analyte datacan be determined based on the analyte database. The time period mayvary based on a number of factors including, but not limited to, thetarget, the analyte being detected, temporal factors (for example timeof day, the day(s) of the week, month or year), and other factors.

The time period over which the analyte data is collected can be measuredin hours, days, months or even years. In one embodiment, the time periodcan be selected to minimize or avoid collecting analyte dataencompassing natural or non-abnormal variations in the analyte of thetarget that may occur and that may not indicate an actual or possibleabnormal condition. In another embodiment, the time period that isselected may include collecting analyte data that encompasses natural ornormal variations in the analyte of the target that may occur whether ornot the collected analyte data indicates an actual or possible abnormalcondition.

The analyte data is collected using non-invasive analyte sensors thatdetect an analyte in the target via spectroscopic techniques usingnon-optical frequencies such as in the radio or microwave frequencyrange of the electromagnetic spectrum or optical frequencies in thevisible range of the electromagnetic spectrum. In one embodiment, theanalyte sensors described herein can be used for in vivo detection ofthe analyte data or used for in vitro detection of the analyte data fromthe target.

In one embodiment, data may also be collected from the target using asecond sensor where the data from the second sensor together with theanalyte data collected by the analyte sensor, can be used to predict anactual or possible abnormal (or normal) condition of the target.

In one embodiment, the techniques described herein can be used on humanor animal subjects for determining an abnormal (or alternatively anormal) medical pathology. For example, in one embodiment, a methoddescribed herein can include establishing an analyte database that isbased on analyte data that has been obtained from subjects bynon-invasive analyte sensors that conducted a plurality of analytesensing routines on the subjects to obtain the analyte data from thesubjects over a period of time including, but not limited to, at leasttwenty four hours, the analyte data containing information on at leastone analyte in the subjects, where the at least one analyte is anindicator of an abnormal medical pathology. Each non-invasive analytesensor includes a detector array having at least one transmit elementand at least one receive element, and for each sensing routine of theplurality of sensing routines the at least one transmit element ispositioned and arranged to transmit an electromagnetic transmit signalinto the corresponding subject, and the at least one receive element ispositioned and arranged to detect a response resulting from transmissionof the electromagnetic transmit signal by the at least one transmitelement into the corresponding subject. A transmit circuit iselectrically connectable to the at least one transmit element, where thetransmit circuit is configured to generate the electromagnetic transmitsignal to be transmitted by the at least one transmit element, and theelectromagnetic transmit signal is in a radio frequency or visible rangeof the electromagnetic spectrum. In addition, a receive circuit iselectrically connectable to the at least one receive element, where thereceive circuit is configured to receive the response detected by the atleast one receive element.

Once the analyte database is established, new analyte data can beobtained from a subject by a non-invasive analyte sensor. The analytedatabase can be updated based on the new analyte data, and the newanalyte data can be analyzed based on the analyte database.

In another embodiment, analyte data obtained over a period of time froma single target using one or more of the analyte sensors describedherein can be used to establish an analyte database whereby the analytedatabase is specific to a single target. Additional analyte data canthen be obtained from the target, the analyte database updated with theadditional analyte data.

In another embodiment, an analytics system described herein can includethe analyte database and at least one of the non-invasive analytesensors.

DRAWINGS

FIG. 1 is a schematic depiction of an analyte sensor system with anon-invasive analyte sensor relative to a target according to anembodiment.

FIGS. 2A-C illustrate different example orientations of antenna arraysthat can be used in an embodiment of a sensor system described herein.

FIGS. 3A-3C illustrate different examples of transmit and receiveantennas with different geometries.

FIGS. 4A, 4B, 4C and 4D illustrate additional examples of differentshapes that the ends of the transmit and receive antennas can have.

FIG. 5 illustrates another example of an antenna array that can be used.

FIG. 6 is a schematic depiction of a portion of another embodiment of ananalyte sensor system with an analyte sensor that uses electromagneticenergy in the form of light to perform analyte sensing described herein.

FIG. 7 illustrates another example of an analyte sensor system with ananalyte sensor that uses electromagnetic energy in the form of light toperform analyte sensing described herein.

FIG. 8 depicts an example operation of the sensor system of FIG. 6.

FIG. 9 illustrates another embodiment of an analyte sensor system with anon-invasive analyte sensor according to an embodiment.

FIG. 10 illustrates another embodiment of an analyte sensor system witha non-invasive analyte sensor according to an embodiment.

FIG. 11 illustrates another embodiment of an analyte sensor system witha non-invasive analyte sensor relative to a target according to anembodiment.

FIG. 12 illustrates another embodiment of an analyte sensor system witha non-invasive analyte sensor relative to a target according to anembodiment.

FIG. 13 is a flowchart of a method for detecting an analyte according toan embodiment.

FIG. 14 is a flowchart of analysis of a response according to anembodiment.

FIG. 15 is a schematic depiction of predictive medical analytics systemdescribed herein.

FIG. 16 is a schematic depiction of a method of establishing an analytedatabase and predicting a condition of a target described herein.

FIG. 17 is a schematic depiction of a method of establishing an analytedatabase using analyte data from a single target.

Like reference numbers represent like parts throughout.

DETAILED DESCRIPTION

The following is a detailed description of using analyte data that hasbeen collected from targets (or from a single target) by analytesensors, for example non-invasive analyte sensors, to establish ananalyte database and using the analyte database to analyze data obtainedfrom a target using an analyte sensor, for example a non-invasiveanalyte sensor. Once the analyte database is established, the analytedatabase can be updated with new analyte data that is collected, and theanalyte database can be used to analyze the new analyte data to deriveinformation from the new analyte data. The information can be used topredict or derive an actual or possible condition (abnormal or normal)of the target.

The analyte data stored in the analyte database may be raw, unprocesseddata that is obtained by the analyte sensor(s). Raw unprocessed data isdata that is obtained by the analyte sensor(s) and that is not processedby the analyte sensor(s) and that does not undergo any other processingprior to being stored in the analyte database. The raw, unprocessed datamay then be analyzed to extract out data on the analyte such as thepresence of the analyte and/or a concentration of the analyte. Theanalyte data stored in the analyte database may alternatively beprocessed data regarding the analyte such as the presence of the analyteand/or a concentration of the analyte, where the processed data resultsfrom processing of raw unprocessed data by the analyte sensor(s) and/orby another device prior to being stored in the analyte database. Theanalyte data stored in the database may also be a combination of raw,unprocessed data and processed data.

The analyte data used to establish the analyte database is obtained overa period of time from a plurality of targets or from a single target.The targets can be human or animal subjects (or collectively subjects),a plurality of animate or inanimate materials, or a plurality of otherobjects. The targets used to establish the analyte database are similarto one another. For example, the targets can be humans; the targets canbe the same kind of animal such as dogs (or breed of dogs); the targetscan the same kind of trees (such as apple trees) or the same kind offluid such as fuel, oil, hydraulic fluid, edible or potable liquids, orthe like.

The analyte data that is collected contains information on at least oneanalyte in the targets. In an example where the targets are human oranimal subjects, the analyte may be an indicator of an abnormal (ornormal) medical pathology of the subjects. In an example where thetargets are animate or inanimate materials, the analyte may be anindicator of an abnormal (or normal) condition of the materials such as,but not limited to, a contaminant or other impurity in the materials, adisease condition of the materials, a mineral in soil, and many othersconditions.

The analyte data, both for establishing the analyte database andsubsequent analyte data for updating the database and for analyzing, maybe collected using non-invasive analyte sensors that detect an analytein the targets via spectroscopic techniques using non-opticalfrequencies such as in the radio or microwave frequency range of theelectromagnetic spectrum or optical frequencies in the visible range ofthe electromagnetic spectrum. The analyte sensors described herein canbe used for in vivo detection of the analyte and in vitro detection ofthe analyte.

One or more analytes can be detected. The analyte(s) that is detected isan indicator of a condition (abnormal or normal) of the target. Forexample, when the target is a human, the analyte can be an indicator ofan abnormal medical pathology of the human target. For example, theanalyte can include, but is not limited to, one or more of glucose,ketones, C-reactive proteins, alcohol, white blood cells, luteinizinghormone or any other analyte that is an indicator of an actual orpossible abnormal medical pathology of the human target. The abnormalmedical pathology can include, but is not limited to, pre-diabetes,diabetes, cancer, cirrhosis and other medical pathologies that can bepredicted based on one or more detectable analytes from the humantarget.

The time period over which the analyte data (both for establishing theanalyte database and subsequent analyte data collection) is collectedmay vary based on a number of factors including, but not limited to, thetarget, the analyte being detected, temporal factors (for example timeof day, the day(s) of the week, month or year), and other factors. Thetime period over which the analyte data is collected can be measured inhours, days, months or even years. In one embodiment, the time periodcan be selected to minimize or avoid collecting analyte dataencompassing natural or non-abnormal variations in the analyte of thetarget(s) that may occur and that may not indicate an actual or possibleabnormal (or normal) condition of the target. In another embodiment, thetime period that is selected may include collecting analyte data thatencompasses natural or normal variations in the analyte of the targetsthat may occur that may not indicate an actual or possible abnormalcondition.

In one embodiment, data may also be collected from the target(s) using asecond sensor where the data from the second sensor, together with theanalyte data collected by the analyte sensor(s), can be used to predictan actual or possible condition of the target. In another embodiment,analyte data may also be collected from one or more additional targetsand the collected analyte data of each target may be used to predict anactual or possible condition of the respective target.

The analyte(s) may be detected via spectroscopic techniques usingnon-optical frequencies such as in the radio or microwave frequencybands of the electromagnetic spectrum or optical frequencies in thevisible range of the electromagnetic spectrum. An analyte sensordescribed herein includes a detector array having at least one transmitelement and at least one receive element. The transmit element and thereceive element can be antennas (FIGS. 1-5) or light emitting elementssuch as light emitting diodes (FIGS. 6-8). In the following description,the transmit element and the receive element, whether they are antennasor light emitting diodes, may each be referred to as a detector element.

The following description together with FIGS. 1-5 will initiallydescribe the analyte sensor system as including a detector array havingtwo or more antennas. Later in the following description, together withFIGS. 6-8, the analyte sensor system is described as including adetector array that includes two or more light emitting devices such aslight emitting diodes (LEDs). The detector array having two or more LEDsmay also be described as an LED array. FIG. 9 illustrates an analytesensor system with a non-invasive analyte sensor in the form of a bodywearable sensor, for example worn around the wrist. FIG. 10 illustratesan analyte sensor system with a non-invasive analyte sensor in the formof a tabletop device. FIG. 11 illustrates an analyte sensor system witha non-invasive analyte sensor in the form of an in vitro sensor usedwith in vitro targets. FIG. 12 illustrates an analyte sensor system witha non-invasive analyte sensor that can be used with industrialprocesses.

For sake of convenience, the following description may describe thetarget(s) as being a human or animal subject, and the condition of thesubject as being an abnormal medical pathology of the subject. However,the targets are not limited to human or animal subjects, and thecondition is not limited to abnormal medical pathologies. The targetscan be any objects from which one or more analytes can be detected usingthe analyte sensors described herein. In addition, the condition that ispredicted can be any normal or abnormal condition of an object.Additional examples of conditions can include, but are not limited to,the presence or absence of a contaminant or other impurity in the targetwhich may be a gas, liquid, solid, gel, and combinations thereof; adisease condition or lack of a disease condition of the target; amineral or lack of mineral in soil; and many others.

In one embodiment, the presence of at least one analyte in a target canbe detected. In another embodiment, an amount or a concentration of theat least one analyte in the target can be determined. The target can beany target containing at least one analyte of interest that one may wishto detect and which indicates an actual or possible abnormal or normalcondition, such as an abnormal medical pathology. The target can be ahuman or animal. In another embodiment, an analyte can be detected froma non-human or non-animal subject, for example a plant or tree, and thedetected analyte can indicate an abnormal condition of the target, forexample a disease in the case of a plant or tree. The analyte can bedetected from a fluid, for example blood, interstitial fluid, cerebralspinal fluid, lymph fluid or urine; human tissue; animal tissue, planttissue, an inanimate object, soil, genetic material, or a microbe.

The detection by the sensors described herein can be non-invasivemeaning that the sensor remains outside the target, such as the humanbody, and the detection of the analyte occurs without requiring removalof fluid or other removal from the target, such as the human body. Inthe case of sensing in the human body, this non-invasive sensing mayalso be referred to as in vivo sensing. In other embodiments, thesensors described herein may be an in vitro sensor where the targetcontaining the analyte has been removed from its host, for example froma human body.

The analyte(s) can be any analyte that one may wish to detect that mayindicate an actual or possible abnormal or normal condition, such as anabnormal medical pathology. For example, in the case of a human target,the analyte(s) can include, but is not limited to, one or more ofglucose, blood glucose, ketones, C-reactive proteins; blood alcohol,white blood cells, or luteinizing hormone. The analyte(s) can include,but is not limited to, a chemical, a combination of chemicals, a virus,a bacteria, or the like. The analyte can be a chemical included inanother medium, with non-limiting examples of such media including afluid containing the at least one analyte, for example blood,interstitial fluid, cerebral spinal fluid, lymph fluid or urine, humantissue, animal tissue, plant tissue, an inanimate object, soil, geneticmaterial, or a microbe. The analyte(s) may also be a non-human,non-biological particle such as a mineral or a contaminant.

The analyte(s) can include, for example, naturally occurring substances,artificial substances, metabolites, and/or reaction products. Asnon-limiting examples, the at least one analyte can include, but is notlimited to, insulin, acarboxyprothrombin; acylcarnitine; adeninephosphoribosyl transferase; adenosine deaminase; albumin;alpha-fetoprotein; amino acid profiles (arginine (Krebs cycle),histidine/urocanic acid, homocysteine, phenylalanine/tyrosine,tryptophan); andrenostenedione; antipyrine; arabinitol enantiomers;arginase; benzoylecgonine (cocaine); biotinidase; biopterin; c-reactiveprotein; carnitine; pro-BNP; BNP; troponin; carnosinase; CD4;ceruloplasmin; chenodeoxycholic acid; chloroquine; cholesterol;cholinesterase; conjugated 1-β hydroxy-cholic acid; cortisol; creatinekinase; creatine kinase MM isoenzyme; cyclosporin A; d-penicillamine;de-ethylchloroquine; dehydroepiandrosterone sulfate; DNA (acetylatorpolymorphism, alcohol dehydrogenase, alpha 1-antitrypsin, cysticfibrosis, Duchenne/Becker muscular dystrophy, analyte-6-phosphatedehydrogenase, hemoglobin A, hemoglobin S, hemoglobin C, hemoglobin D,hemoglobin E, hemoglobin F, D-Punjab, beta-thalassemia, hepatitis Bvirus, HCMV, HIV-1, HTLV-1, Leber hereditary optic neuropathy, MCAD,RNA, PKU, Plasmodium vivax, sexual differentiation, 21-deoxycortisol);desbutylhalofantrine; dihydropteridine reductase; diptheria/tetanusantitoxin; erythrocyte arginase; erythrocyte protoporphyrin; esterase D;fatty acids/acylglycines; free 3-human chorionic gonadotropin; freeerythrocyte porphyrin; free thyroxine (FT4); free tri-iodothyronine(FT3); fumarylacetoacetase; galactose/gal-1-phosphate;galactose-1-phosphate uridyltransferase; gentamicin; analyte-6-phosphatedehydrogenase; glutathione; glutathione perioxidase; glycocholic acid;glycosylated hemoglobin; halofantrine; hemoglobin variants;hexosaminidase A; human erythrocyte carbonic anhydrase I;17-alpha-hydroxyprogesterone; hypoxanthine phosphoribosyl transferase;immunoreactive trypsin; lactate; lead; lipoproteins ((a), B/A-1, β);lysozyme; mefloquine; netilmicin; phenobarbitone; phenytoin;phytanic/pristanic acid; progesterone; prolactin; prolidase; purinenucleoside phosphorylase; quinine; reverse tri-iodothyronine (rT3);selenium; serum pancreatic lipase; sissomicin; somatomedin C; specificantibodies (adenovirus, anti-nuclear antibody, anti-zeta antibody,arbovirus, Aujeszky's disease virus, dengue virus, Dracunculusmedinensis, Echinococcus granulosus, Entamoeba histolytica, enterovirus,Giardia duodenalisa, Helicobacter pylori, hepatitis B virus, herpesvirus, HIV-1, IgE (atopic disease), influenza virus, Leishmaniadonovani, leptospira, measles/mumps/rubella, Mycobacterium leprae,Mycoplasma pneumoniae, Myoglobin, Onchocerca volvulus, parainfluenzavirus, Plasmodium falciparum, polio virus, Pseudomonas aeruginosa,respiratory syncytial virus, rickettsia (scrub typhus), Schistosomamansoni, Toxoplasma gondii, Trepenoma pallidium, Trypanosomacruzi/rangeli, vesicular stomatis virus, Wuchereria bancrofti, yellowfever virus); specific antigens (hepatitis B virus, HIV-1);succinylacetone; sulfadoxine; theophylline; thyrotropin (TSH); thyroxine(T4); thyroxine-binding globulin; trace elements; transferrin;UDP-galactose-4-epimerase; urea; uroporphyrinogen I synthase; vitamin A;white blood cells; and zinc protoporphyrin.

The analyte(s) can also include one or more chemicals introduced intothe target. The analyte(s) can include a marker such as a contrastagent, a radioisotope, or other chemical agent. The analyte(s) caninclude a fluorocarbon-based synthetic blood. The analyte(s) can includea drug or pharmaceutical composition, with non-limiting examplesincluding ethanol; cannabis (marijuana, tetrahydrocannabinol, hashish);inhalants (nitrous oxide, amyl nitrite, butyl nitrite,chlorohydrocarbons, hydrocarbons); cocaine (crack cocaine); stimulants(amphetamines, methamphetamines, Ritalin, Cylert, Preludin, Didrex,PreState, Voranil, Sandrex, Plegine); depressants (barbiturates,methaqualone, tranquilizers such as Valium, Librium, Miltown, Serax,Equanil, Tranxene); hallucinogens (phencyclidine, lysergic acid,mescaline, peyote, psilocybin); narcotics (heroin, codeine, morphine,opium, meperidine, Percocet, Percodan, Tussionex, Fentanyl, Darvon,Talwin, Lomotil); designer drugs (analogs of fentanyl, meperidine,amphetamines, methamphetamines, and phencyclidine, for example,Ecstasy); anabolic steroids; and nicotine. The analyte(s) can includeother drugs or pharmaceutical compositions. The analyte(s) can includeneurochemicals or other chemicals generated within the body, such as,for example, ascorbic acid, uric acid, dopamine, noradrenaline,3-methoxytyramine (3MT), 3,4-Dihydroxyphenylacetic acid (DOPAC),Homovanillic acid (HVA), 5-Hydroxytryptamine (5HT), and5-Hydroxyindoleacetic acid (FHIAA).

The sensor systems described herein operate by transmitting anelectromagnetic signal (whether in the radio or microwave frequencyrange of the electromagnetic spectrum in FIGS. 1-5 and 9-12 or in thevisible range of the electromagnetic spectrum in FIGS. 6-8) toward andinto a target using a transmit element such as a transmit antenna or atransmit LED. A returning signal that results from the transmission ofthe transmitted signal is detected by a receive element such as areceive antenna or a photodetector. The signal(s) detected by thereceive element can be analyzed to detect the analyte based on theintensity of the received signal(s) and reductions in intensity at oneor more frequencies where the analyte absorbs the transmitted signal.

FIGS. 1-5 illustrate a non-invasive analyte sensor system that uses twoor more antennas including a transmit antenna and a receive antenna. Thetransmit antenna and the receive antenna can be located near the targetand operated as further described herein to assist in detecting at leastone analyte in the target. The transmit antenna transmits a signal,which has at least two frequencies in the radio or microwave frequencyrange, toward and into the target. The signal with the at least twofrequencies can be formed by separate signal portions, each having adiscrete frequency, that are transmitted separately at separate times ateach frequency. In another embodiment, the signal with the at least twofrequencies may be part of a complex signal that includes a plurality offrequencies including the at least two frequencies. The complex signalcan be generated by blending or multiplexing multiple signals togetherfollowed by transmitting the complex signal whereby the plurality offrequencies are transmitted at the same time. One possible technique forgenerating the complex signal includes, but is not limited to, using aninverse Fourier transformation technique. The receive antenna detects aresponse resulting from transmission of the signal by the transmitantenna into the target containing the at least one analyte of interest.

The transmit antenna and the receive antenna are decoupled (which mayalso be referred to as detuned or the like) from one another. Decouplingrefers to intentionally fabricating the configuration and/or arrangementof the transmit antenna and the receive antenna to minimize directcommunication between the transmit antenna and the receive antenna,preferably absent shielding. Shielding between the transmit antenna andthe receive antenna can be utilized. However, the transmit antenna andthe receive antenna are decoupled even without the presence ofshielding.

An example of detecting an analyte using a non-invasive spectroscopysensor operating in the radio or microwave frequency range of theelectromagnetic spectrum is described in WO 2019/217461, the entirecontents of which are incorporated herein by reference. The signal(s)detected by the receive antenna can be complex signals including aplurality of signal components, each signal component being at adifferent frequency. In an embodiment, the detected complex signals canbe decomposed into the signal components at each of the differentfrequencies, for example through a Fourier transformation. In anembodiment, the complex signal detected by the receive antenna can beanalyzed as a whole (i.e. without demultiplexing the complex signal) todetect the analyte as long as the detected signal provides enoughinformation to make the analyte detection. In addition, the signal(s)detected by the receive antenna can be separate signal portions, eachhaving a discrete frequency.

Referring now to FIG. 1, an embodiment of a non-invasive analyte sensorsystem with a non-invasive analyte sensor 5 is illustrated. The sensor 5is depicted relative to a target 7 (in this example in the form of ahuman or animal) that contains an analyte of interest 9. In thisexample, the sensor 5 is depicted as including an antenna array thatincludes a transmit antenna/element 11 (hereinafter “transmit antenna11”) and a receive antenna/element 13 (hereinafter “receive antenna13”). The sensor 5 further includes a transmit circuit 15, a receivecircuit 17, and a controller 19. As discussed further below, the sensor5 can also include a power supply, such as a battery (not shown in FIG.1). In some embodiments, power can be provided from mains power, forexample by plugging the sensor 5 into a wall socket via a cord connectedto the sensor 5. The sensor 5 may be configured as a wearable devicethat is configured to be worn around the wrist (see FIG. 9), configuredas a table top device (FIG. 10), used in an in vitro detector (see FIG.11), or used in a non-human/animal version for example detection in anindustrial process such as in a flowing fluid (see FIG. 12).

The transmit antenna 11 is positioned, arranged and configured totransmit a signal 21 that is in the radio frequency (RF) or microwaverange of the electromagnetic spectrum into the target 7. The transmitantenna 11 can be an electrode or any other suitable transmitter ofelectromagnetic signals in the radio frequency (RF) or microwave range.The transmit antenna 11 can have any arrangement and orientationrelative to the target 7 that is sufficient to allow the analyte sensingto take place. In one non-limiting embodiment, the transmit antenna 11can be arranged to face in a direction that is substantially toward thetarget 7.

The signal 21 transmitted by the transmit antenna 11 is generated by thetransmit circuit 15 which is electrically connectable to the transmitantenna 11. The transmit circuit 15 can have any configuration that issuitable to generate a transmit signal to be transmitted by the transmitantenna 11. Transmit circuits for generating transmit signals in the RFor microwave frequency range are well known in the art. In oneembodiment, the transmit circuit 15 can include, for example, aconnection to a power source, a frequency generator, and optionallyfilters, amplifiers or any other suitable elements for a circuitgenerating an RF or microwave frequency electromagnetic signal. In anembodiment, the signal generated by the transmit circuit 15 can have atleast two discrete frequencies (i.e. a plurality of discretefrequencies), each of which is in the range from about 10 kHz to about100 GHz. In another embodiment, each of the at least two discretefrequencies can be in a range from about 300 MHz to about 6000 MHz. Inan embodiment, the transmit circuit 15 can be configured to sweepthrough a range of frequencies that are within the range of about 10 kHzto about 100 GHz, or in another embodiment a range of about 300 MHz toabout 6000 MHz. In an embodiment, the transmit circuit 15 can beconfigured to produce a complex transmit signal, the complex signalincluding a plurality of signal components, each of the signalcomponents having a different frequency. The complex signal can begenerated by blending or multiplexing multiple signals together followedby transmitting the complex signal whereby the plurality of frequenciesare transmitted at the same time.

The receive antenna 13 is positioned, arranged, and configured to detectone or more electromagnetic response signals 23 that result from thetransmission of the transmit signal 21 by the transmit antenna 11 intothe target 7 and impinging on the analyte 9. The receive antenna 13 canbe an electrode or any other suitable receiver of electromagneticsignals in the radio frequency (RF) or microwave range. In anembodiment, the receive antenna 13 is configured to detectelectromagnetic signals having at least two frequencies, each of whichis in the range from about 10 kHz to about 100 GHz, or in anotherembodiment a range from about 300 MHz to about 6000 MHz. The receiveantenna 13 can have any arrangement and orientation relative to thetarget 7 that is sufficient to allow detection of the response signal(s)23 to allow the analyte sensing to take place. In one non-limitingembodiment, the receive antenna 13 can be arranged to face in adirection that is substantially toward the target 7.

The receive circuit 17 is electrically connectable to the receiveantenna 13 and conveys the received response from the receive antenna 13to the controller 19. The receive circuit 17 can have any configurationthat is suitable for interfacing with the receive antenna 13 to convertthe electromagnetic energy detected by the receive antenna 13 into oneor more signals reflective of the response signal(s) 23. Theconstruction of receive circuits are well known in the art. The receivecircuit 17 can be configured to condition the signal(s) prior toproviding the signal(s) to the controller 19, for example throughamplifying the signal(s), filtering the signal(s), or the like.Accordingly, the receive circuit 17 may include filters, amplifiers, orany other suitable components for conditioning the signal(s) provided tothe controller 19. In an embodiment, at least one of the receive circuit17 or the controller 19 can be configured to decompose or demultiplex acomplex signal, detected by the receive antenna 13, including aplurality of signal components each at different frequencies into eachof the constituent signal components. In an embodiment, decomposing thecomplex signal can include applying a Fourier transform to the detectedcomplex signal. However, decomposing or demultiplexing a receivedcomplex signal is optional. Instead, in an embodiment, the complexsignal detected by the receive antenna can be analyzed as a whole (i.e.without demultiplexing the complex signal) to detect the analyte as longas the detected signal provides enough information to make the analytedetection.

The controller 19 controls the operation of the sensor 5. The controller19, for example, can direct the transmit circuit 15 to generate atransmit signal to be transmitted by the transmit antenna 11. Thecontroller 19 further receives signals from the receive circuit 17. Thecontroller 19 can optionally process the signals from the receivecircuit 17 to detect the analyte(s) 9 in the target 7. In oneembodiment, the controller 19 may optionally be in communication with atleast one external device 25 such as a user device and/or a remoteserver 27, for example through one or more wireless connections such asBluetooth, wireless data connections such a 4G, 5G, LTE or the like, orWi-Fi. If provided, the external device 25 and/or remote server 27 mayprocess (or further process) the signals that the controller 19 receivesfrom the receive circuit 17, for example to detect the analyte(s) 9 anddevelop the analyte database. If provided, the external device 25 may beused to provide communication between the sensor 5 and the remote server27, for example using a wired data connection or via a wireless dataconnection or Wi-Fi of the external device 25 to provide the connectionto the remote server 27.

With continued reference to FIG. 1, the sensor 5 may include a sensorhousing 29 (shown in dashed lines) that defines an interior space 31.Components of the sensor 5 may be attached to and/or disposed within thehousing 29. For example, the transmit antenna 11 and the receive antenna13 are attached to the housing 29. In some embodiments, the antennas 11,13 may be entirely or partially within the interior space 31 of thehousing 29. In some embodiments, the antennas 11, 13 may be attached tothe housing 29 but at least partially or fully located outside theinterior space 31. In some embodiments, the transmit circuit 15, thereceive circuit 17 and the controller 19 are attached to the housing 29and disposed entirely within the sensor housing 29.

The receive antenna 13 is decoupled or detuned with respect to thetransmit antenna 11 such that electromagnetic coupling between thetransmit antenna 11 and the receive antenna 13 is reduced. Thedecoupling of the transmit antenna 11 and the receive antenna 13increases the portion of the signal(s) detected by the receive antenna13 that is the response signal(s) 23 from the target 7, and minimizesdirect receipt of the transmitted signal 21 by the receive antenna 13.The decoupling of the transmit antenna 11 and the receive antenna 13results in transmission from the transmit antenna 11 to the receiveantenna 13 having a reduced forward gain (S21) and an increasedreflection at output (S22) compared to antenna systems having coupledtransmit and receive antennas.

In an embodiment, coupling between the transmit antenna 11 and thereceive antenna 13 is 95% or less. In another embodiment, couplingbetween the transmit antenna 11 and the receive antenna 13 is 90% orless. In another embodiment, coupling between the transmit antenna 11and the receive antenna 13 is 85% or less. In another embodiment,coupling between the transmit antenna 11 and the receive antenna 13 is75% or less.

Any technique for reducing coupling between the transmit antenna 11 andthe receive antenna 13 can be used. For example, the decoupling betweenthe transmit antenna 11 and the receive antenna 13 can be achieved byone or more intentionally fabricated configurations and/or arrangementsbetween the transmit antenna 11 and the receive antenna 13 that issufficient to decouple the transmit antenna 11 and the receive antenna13 from one another.

For example, in one embodiment described further below, the decouplingof the transmit antenna 11 and the receive antenna 13 can be achieved byintentionally configuring the transmit antenna 11 and the receiveantenna 13 to have different geometries from one another. Intentionallydifferent geometries refers to different geometric configurations of thetransmit and receive antennas 11, 13 that are intentional. Intentionaldifferences in geometry are distinct from differences in geometry oftransmit and receive antennas that may occur by accident orunintentionally, for example due to manufacturing errors or tolerances.

Another technique to achieve decoupling of the transmit antenna 11 andthe receive antenna 13 is to provide appropriate spacing between eachantenna 11, 13 that is sufficient to decouple the antennas 11, 13 andforce a proportion of the electromagnetic lines of force of thetransmitted signal 21 into the target 7 thereby minimizing oreliminating as much as possible direct receipt of electromagnetic energyby the receive antenna 13 directly from the transmit antenna 11 withouttraveling into the target 7. The appropriate spacing between eachantenna 11, 13 can be determined based upon factors that include, butare not limited to, the output power of the signal from the transmitantenna 11, the size of the antennas 11, 13, the frequency orfrequencies of the transmitted signal, and the presence of any shieldingbetween the antennas. This technique helps to ensure that the responsedetected by the receive antenna 13 is measuring the analyte 9 and is notjust the transmitted signal 21 flowing directly from the transmitantenna 11 to the receive antenna 13. In some embodiments, theappropriate spacing between the antennas 11, 13 can be used togetherwith the intentional difference in geometries of the antennas 11, 13 toachieve decoupling.

In one embodiment, the transmit signal that is transmitted by thetransmit antenna 11 can have at least two different frequencies, forexample upwards of 7 to 12 different and discrete frequencies. Inanother embodiment, the transmit signal can be a series of discrete,separate signals with each separate signal having a single frequency ormultiple different frequencies.

In one embodiment, the transmit signal (or each of the transmit signals)can be transmitted over a transmit time that is less than, equal to, orgreater than about 300 ms. In another embodiment, the transmit time canbe less than, equal to, or greater than about 200 ms. In still anotherembodiment, the transmit time can be less than, equal to, or greaterthan about 30 ms. The transmit time could also have a magnitude that ismeasured in seconds, for example 1 second, 5 seconds, 10 seconds, ormore. In an embodiment, the same transmit signal can be transmittedmultiple times, and then the transmit time can be averaged. In anotherembodiment, the transmit signal (or each of the transmit signals) can betransmitted with a duty cycle that is less than or equal to about 50%.

FIGS. 2A-2C illustrate examples of antenna arrays 33 that can be used inthe sensor system 5 and how the antenna arrays 33 can be oriented. Manyorientations of the antenna arrays 33 are possible, and any orientationcan be used as long as the sensor 5 can perform its primary function ofsensing the analyte 9.

In FIG. 2A, the antenna array 33 includes the transmit antenna 11 andthe receive antenna 13 disposed on a substrate 35 which may besubstantially planar. This example depicts the array 33 disposedsubstantially in an X-Y plane. In this example, dimensions of theantennas 11, 13 in the X and Y-axis directions can be considered lateraldimensions, while a dimension of the antennas 11, 13 in the Z-axisdirection can be considered a thickness dimension. In this example, eachof the antennas 11, 13 has at least one lateral dimension (measured inthe X-axis direction and/or in the Y-axis direction) that is greaterthan the thickness dimension thereof (in the Z-axis direction). In otherwords, the transmit antenna 11 and the receive antenna 13 are eachrelatively flat or of relatively small thickness in the Z-axis directioncompared to at least one other lateral dimension measured in the X-axisdirection and/or in the Y-axis direction.

In use of the embodiment in FIG. 2A, the sensor and the array 33 may bepositioned relative to the target 7 such that the target 7 is below thearray 33 in the Z-axis direction or above the array 33 in the Z-axisdirection whereby one of the faces of the antennas 11, 13 face towardthe target 7. Alternatively, the target 7 can be positioned to the leftor right sides of the array 33 in the X-axis direction whereby one ofthe ends of each one of the antennas 11, 13 face toward the target 7.Alternatively, the target 7 can be positioned to the sides of the array33 in the Y-axis direction whereby one of the sides of each one of theantennas 11, 13 face toward the target 7.

The sensor 5 can also be provided with one or more additional antennaarrays in addition the antenna array 33. For example, FIG. 2A alsodepicts an optional second antenna array 33 a that includes the transmitantenna 11 and the receive antenna 13 disposed on a substrate 35 a whichmay be substantially planar. Like the array 33, the array 33 a may alsobe disposed substantially in the X-Y plane, with the arrays 33, 33 aspaced from one another in the X-axis direction.

In FIG. 2B, the antenna array 33 is depicted as being disposedsubstantially in the Y-Z plane. In this example, dimensions of theantennas 11, 13 in the Y and Z-axis directions can be considered lateraldimensions, while a dimension of the antennas 11, 13 in the X-axisdirection can be considered a thickness dimension. In this example, eachof the antennas 11, 13 has at least one lateral dimension (measured inthe Y-axis direction and/or in the Z-axis direction) that is greaterthan the thickness dimension thereof (in the X-axis direction). In otherwords, the transmit antenna 11 and the receive antenna 13 are eachrelatively flat or of relatively small thickness in the X-axis directioncompared to at least one other lateral dimension measured in the Y-axisdirection and/or in the Z-axis direction.

In use of the embodiment in FIG. 2B, the sensor and the array 33 may bepositioned relative to the target 7 such that the target 7 is below thearray 33 in the Z-axis direction or above the array 33 in the Z-axisdirection whereby one of the ends of each one of the antennas 11, 13face toward the target 7. Alternatively, the target 7 can be positionedin front of or behind the array 33 in the X-axis direction whereby oneof the faces of each one of the antennas 11, 13 face toward the target7. Alternatively, the target 7 can be positioned to one of the sides ofthe array 33 in the Y-axis direction whereby one of the sides of eachone of the antennas 11, 13 face toward the target 7.

In FIG. 2C, the antenna array 33 is depicted as being disposedsubstantially in the X-Z plane. In this example, dimensions of theantennas 11, 13 in the X and Z-axis directions can be considered lateraldimensions, while a dimension of the antennas 11, 13 in the Y-axisdirection can be considered a thickness dimension. In this example, eachof the antennas 11, 13 has at least one lateral dimension (measured inthe X-axis direction and/or in the Z-axis direction) that is greaterthan the thickness dimension thereof (in the Y-axis direction). In otherwords, the transmit antenna 11 and the receive antenna 13 are eachrelatively flat or of relatively small thickness in the Y-axis directioncompared to at least one other lateral dimension measured in the X-axisdirection and/or in the Z-axis direction.

In use of the embodiment in FIG. 2C, the sensor and the array 33 may bepositioned relative to the target 7 such that the target 7 is below thearray 33 in the Z-axis direction or above the array 33 in the Z-axisdirection whereby one of the ends of each one of the antennas 11, 13face toward the target 7. Alternatively, the target 7 can be positionedto the left or right sides of the array 33 in the X-axis directionwhereby one of the sides of each one of the antennas 11, 13 face towardthe target 7. Alternatively, the target 7 can be positioned in front ofor in back of the array 33 in the Y-axis direction whereby one of thefaces of each one of the antennas 11, 13 face toward the target 7.

The arrays 33, 33 a in FIGS. 2A-2C need not be oriented entirely withina plane such as the X-Y plane, the Y-Z plane or the X-Z plane. Instead,the arrays 33, 33 a can be disposed at angles to the X-Y plane, the Y-Zplane and the X-Z plane.

Decoupling Antennas Using Differences in Antenna Geometries

As mentioned above, one technique for decoupling the transmit antenna 11from the receive antenna 13 is to intentionally configure the transmitantenna 11 and the receive antenna 13 to have intentionally differentgeometries. Intentionally different geometries refers to differences ingeometric configurations of the transmit and receive antennas 11, 13that are intentional, and is distinct from differences in geometry ofthe transmit and receive antennas 11, 13 that may occur by accident orunintentionally, for example due to manufacturing errors or toleranceswhen fabricating the antennas 11, 13.

The different geometries of the antennas 11, 13 may manifest itself, andmay be described, in a number of different ways. For example, in a planview of each of the antennas 11, 13 (such as in FIGS. 3A-C), the shapesof the perimeter edges of the antennas 11, 13 may be different from oneanother. The different geometries may result in the antennas 11, 13having different surface areas in plan view. The different geometriesmay result in the antennas 11, 13 having different aspect ratios in planview (i.e. a ratio of their sizes in different dimensions; for example,as discussed in further detail below, the ratio of the length divided bythe width of the antenna 11 may be different than the ratio of thelength divided by the width for the antenna 13). In some embodiments,the different geometries may result in the antennas 11, 13 having anycombination of different perimeter edge shapes in plan view, differentsurface areas in plan view, and/or different aspect ratios. In someembodiments, the antennas 11, 13 may have one or more holes formedtherein (see FIG. 2B) within the perimeter edge boundary, or one or morenotches formed in the perimeter edge (see FIG. 2B).

So as used herein, a difference in geometry or a difference ingeometrical shape of the antennas 11, 13 refers to any intentionaldifference in the figure, length, width, size, shape, area closed by aboundary (i.e. the perimeter edge), etc. when the respective antenna 11,13 is viewed in a plan view.

The antennas 11, 13 can have any configuration and can be formed fromany suitable material that allows them to perform the functions of theantennas 11, 13 as described herein. In one embodiment, the antennas 11,13 can be formed by strips of material. A strip of material can includea configuration where the strip has at least one lateral dimensionthereof greater than a thickness dimension thereof when the antenna isviewed in a plan view (in other words, the strip is relatively flat orof relatively small thickness compared to at least one other lateraldimension, such as length or width when the antenna is viewed in a planview as in FIGS. 3A-C). A strip of material can include a wire. Theantennas 11, 13 can be formed from any suitable conductive material(s)including metals and conductive non-metallic materials. Examples ofmetals that can be used include, but are not limited to, copper or gold.Another example of a material that can be used is non-metallic materialsthat are doped with metallic material to make the non-metallic materialconductive.

In FIGS. 2A-2C, the antennas 11, 13 within each one of the arrays 33, 33a have different geometries from one another. In addition, FIGS. 3A-Cillustrate plan views of additional examples of the antennas 11, 13having different geometries from one another. The examples in FIGS.2A-2C and 3A-C are not exhaustive and many different configurations arepossible.

FIG. 3A illustrates a plan view of an antenna array having two antennaswith different geometries. In this example, the antennas 11, 13 areillustrated as substantially linear strips each with a lateral lengthL₁₁, L₁₃, a lateral width W₁₁, W₁₃, and a perimeter edge E₁₁, E₁₃. Theperimeter edges E₁₁, E₁₃ extend around the entire periphery of theantennas 11, 13 and bound an area in plan view. In this example, thelateral length L₁₁, L₁₃ and/or the lateral width W₁₁, W₁₃ is greaterthan a thickness dimension of the antennas 11, 13 extending into/fromthe page when viewing FIG. 3A. In this example, the antennas 11, 13differ in geometry from one another in that the shapes of the ends ofthe antennas 11, 13 differ from one another. For example, when viewingFIG. 3A, the right end 42 of the antenna 11 has a different shape thanthe right end 44 of the antenna 13. Similarly, the left end 46 of theantenna 11 may have a similar shape as the right end 42, but differsfrom the left end 48 of the antenna 13 which may have a similar shape asthe right end 44. It is also possible that the lateral lengths L₁₁, L₁₃and/or the lateral widths W₁₁, W₁₃ of the antennas 11, 13 could differfrom one another.

FIG. 3B illustrates another plan view of an antenna array having twoantennas with different geometries that is somewhat similar to FIG. 3A.In this example, the antennas 11, 13 are illustrated as substantiallylinear strips each with the lateral length L₁₁, L₁₃, the lateral widthW₁₁, W₁₃, and the perimeter edge E₁₁, E₁₃. The perimeter edges E₁₁, E₁₃extend around the entire periphery of the antennas 11, 13 and bound anarea in plan view. In this example, the lateral length L₁₁, L₁₃ and/orthe lateral width W₁₁, W₁₃ is greater than a thickness dimension of theantennas 11, 13 extending into/from the page when viewing FIG. 3B. Inthis example, the antennas 11, 13 differ in geometry from one another inthat the shapes of the ends of the antennas 11, 13 differ from oneanother. For example, when viewing FIG. 3B, the right end 42 of theantenna 11 has a different shape than the right end 44 of the antenna13. Similarly, the left end 46 of the antenna 11 may have a similarshape as the right end 42, but differs from the left end 48 of theantenna 13 which may have a similar shape as the right end 44. Inaddition, the lateral widths W₁₁, W₁₃ of the antennas 11, 13 differ fromone another. It is also possible that the lateral lengths L₁₁, L₁₃ ofthe antennas 11, 13 could differ from one another.

FIG. 3C illustrates another plan view of an antenna array having twoantennas with different geometries that is somewhat similar to FIGS. 3Aand 3B. In this example, the antennas 11, 13 are illustrated assubstantially linear strips each with the lateral length L₁₁, L₁₃, thelateral width W₁₁, W₁₃, and the perimeter edge E₁₁, E₁₃. The perimeteredges E₁₁, E₁₃ extend around the entire periphery of the antennas 11, 13and bound an area in plan view. In this example, the lateral length L₁₁,L₁₃ and/or the lateral width W₁₁, W₁₃ is greater than a thicknessdimension of the antennas 11, 13 extending into/from the page whenviewing FIG. 3C. In this example, the antennas 11, 13 differ in geometryfrom one another in that the shapes of the ends of the antennas 11, 13differ from one another. For example, when viewing FIG. 3C, the rightend 42 of the antenna 11 has a different shape than the right end 44 ofthe antenna 13. Similarly, the left end 46 of the antenna 11 may have asimilar shape as the right end 42, but differs from the left end 48 ofthe antenna 13 which may have a similar shape as the right end 44. Inaddition, the lateral widths W₁₁, W₁₃ of the antennas 11, 13 differ fromone another. It is also possible that the lateral lengths L₁₁, L₁₃ ofthe antennas 11, 13 could differ from one another.

FIGS. 4A-D are plan views of additional examples of different shapesthat the ends of the transmit and receive antennas 11, 13 can have toachieve differences in geometry. Either one of, or both of, the ends ofthe antennas 11, 13 can have the shapes in FIGS. 4A-D, including in theembodiments in FIGS. 3A-C. FIG. 4A depicts the end as being generallyrectangular. FIG. 4B depicts the end as having one rounded corner whilethe other corner remains a right angle. FIG. 4C depicts the entire endas being rounded or outwardly convex. FIG. 4D depicts the end as beinginwardly concave. Many other shapes are possible.

FIG. 5 illustrates another plan view of an antenna array having sixantennas illustrated as substantially linear strips. In this example,the antennas differ in geometry from one another in that the shapes ofthe ends of the antennas, the lateral lengths and/or the lateral widthsof the antennas differ from one another.

Another technique to achieve decoupling of the antennas is to use anappropriate spacing between each antenna with the spacing beingsufficient to force most or all of the signal(s) transmitted by thetransmit antenna into the target, thereby minimizing the direct receiptof electromagnetic energy by the receive antenna directly from thetransmit antenna. The appropriate spacing can be used by itself toachieve decoupling of the antennas. In another embodiment, theappropriate spacing can be used together with differences in geometry ofthe antennas to achieve decoupling.

Referring to FIG. 2A, there is a spacing D between the transmit antenna11 and the receive antenna 13 at the location indicated. The spacing Dbetween the antennas 11, 13 may be constant over the entire length (forexample in the X-axis direction) of each antenna 11, 13, or the spacingD between the antennas 11, 13 could vary. Any spacing D can be used aslong as the spacing D is sufficient to result in most or all of thesignal(s) transmitted by the transmit antenna 11 reaching the target andminimizing the direct receipt of electromagnetic energy by the receiveantenna 13 directly from the transmit antenna 11, thereby decoupling theantennas 11, 13 from one another.

In addition, there is preferably a maximum spacing and a minimum spacingbetween the transmit antenna 11 and the receive antenna 13. The maximumspacing may be dictated by the maximum size of the housing 29. In oneembodiment, the maximum spacing can be about 50 mm. In one embodiment,the minimum spacing can be from about 1.0 mm to about 5.0 mm.

FIG. 9 illustrates an example use of the sensor 5 of FIG. 1 in the formof a body wearable sensor, in particular a watch-like device 90 wornaround the wrist. The sensor 5 is incorporated into a sensor body 92that is fastened to the wrist by a strap 94 that extends around thewrist.

FIG. 10 illustrates an example use of the sensor 5 of FIG. 1 in the formof a tabletop device 100. The term “tabletop” is used interchangeablywith “countertop” and refers to a device that is intended to reside on atop surface of a structure such as, but not limited to, a table,counter, shelf, another device, or the like during use. In someembodiments, the device 100 can be mounted on a vertical wall. Thedevice 100 is configured to obtain a real-time, on-demand reading of ananalyte in a user such as, but not limited to, obtaining a glucose levelreading of the user using the non-invasive analyte sensor 5 incorporatedinto the device 100. The device 100 is illustrated as being generallyrectangular box shaped. However, the device 100 can have other shapessuch as cylindrical, square box, triangular and many other shapes. Thedevice 100 includes a housing 102, a reading area 104, for example on atop surface of the housing 102, where the antennas 11, 13 of the sensor5 are positioned to be able to obtain a reading, and a display screen106, for example on the top surface of the housing 102, for displayingdata such as results of a reading by the sensor 5. Power for the device100 can be provided via a power cord 108 that plugs into a wall socket.The device 100 may also include one or more batteries which act as aprimary power source for the device 100 instead of power provided viathe power cord 108 or the one or more batteries can act as a back-uppower source in the event power is not available via the power cord 108.A reading by the device 100 can be triggered with a trigger button 110.An on/off power button or switch 112 can be provided anywhere on thedevice 100 to power the device 100 on and off. The on/off power buttonor switch 112 could also function as the trigger button instead of thetrigger button 110. Alternatively, the trigger button 110 may act as anon/off power button to power the device 100 on and off, as well astrigger a reading.

FIG. 11 illustrates the sensor 5 of FIG. 1 incorporated into an in vitrosensor 120 that is configured to operate with an in vitro sample that isheld in a sample container 122 that contains a sample to be analyzed,where the container 122 is held in a sample chamber 124. The sensor 120can include additional features that are similar to the features of thehousing disclosed in U.S. Pat. No. 9,041,920 the entire contents ofwhich are incorporated herein by reference.

FIG. 12 illustrates the sensor 5 of FIG. 1 as an in vitro sensor 130 inan industrial process, for example with an in vitro fluid passageway 132through which an in vitro fluid flows as indicated by the arrow A. Thesensor 130 can be positioned outside the passageway 132 as illustrated,or the sensor 130 can be positioned within the passageway 132. Thesensor 130 can be used in any application that can transmit thesignal(s) into a target and receive a response.

FIG. 6 schematically depicts another example of a non-invasive analytesensor 50 that forms a portion of another embodiment of a non-invasiveanalyte sensor system. The non-invasive analyte sensor 50 useselectromagnetic energy in the form of light waves at selectedelectromagnetic frequencies to perform non-invasive analyte sensingdescribed herein. The sensor 50 includes a housing 52 and a sensor arraythat includes a plurality of transmit elements 54 each of which can emitelectromagnetic energy in the form of light. In this example, thetransmit elements 54 are disposed in an array surrounding a receiveelement 56 which can be a photodetector. The illustrated example depictsthe array as having a total of twelve of the elements 54 arranged in acircular array around the receive element 56. However, a larger orsmaller number of the elements 54 can be provided in the array. Inaddition, the array can have an arrangement other than being a circulararray. The separate receive element 56 is not necessary if one of theelements 54 is controlled to function as a receive element as describedin detail below with respect to LEDs that can function to both emitlight and detect light.

FIG. 7 illustrates another embodiment similar to FIG. 6. In FIG. 7, eachof the elements 54 are controlled in a manner whereby any one or more ofthe elements 54 can emit light (and thereby function as a transmitelement) and any one or more of the elements 54 can act as a lightdetector (and thereby function as a receive element). In FIG. 7, sincean element 54 can function as a transmit element or as a receiveelement, the use of a separate receive element 56 as in FIG. 6 is notrequired. However, the separate receive element 56 can be included ifdesired. The illustrated example depicts the array as having a total oftwelve of the elements 54 arranged into a 3×4 or 4×3 array. However, alarger or smaller number of the elements 54 can be provided in thearray. In addition, the array can have other arrangements including theelements 54 being disposed in a circular array.

In one embodiment, the elements 54 in FIGS. 6 and 7 may be lightemitting diodes (LEDs) and the array that includes the LEDs can bereferred to as an LED array. LEDs that can be selectively controlled toemit light (i.e. a photoemitter) or detect light (i.e. a photodetector)are known. See Stojanovic et al., An optical sensing approach based onlight emitting diodes, Journal of Physics: Conference Series 76 (2007);Rossiter et al., A novel tactile sensor using a matrix of LEDs operatingin both photoemitter and photodetector modes, Proc of 4th IEEEInternational Conference on Sensors (IEEE Sensors 2005). See also U.S.Pat. No. 4,202,000 the entire contents of which are incorporated hereinby reference.

Referring to FIG. 8, in the embodiments of FIGS. 6 and 7 some or all theelements 54 may be flush with a surface 58 of the housing 52 so thatlight emitted by each transmit element 54 may be transmitted from thesensor 50 and receive element 56 (or one of the elements 54 acting as areceive element) detects returning light. In another embodiment, some orall of the transmit elements 54 may be recessed within the housing 52but the light from each transit element 54 is suitably channeled to theoutside and returning light suitably channeled to the receive elements54. In still another embodiment, some or all of the transmit elements 54may project (partially or completely) from the surface 58 of the housing52.

In FIGS. 6 and 7, when the elements 54 are LEDs, the LEDs can becontrolled in a manner whereby any one or more of the LEDs can emitlight. In addition, the receive element 56 of FIG. 6 can act as a lightdetector, or any one or more of the LEDs in FIGS. 6 and 7 can becontrolled to act as a light detector. The LEDs that are used preferablypermit at least two different wavelengths of light to be emitted. Inanother embodiment, at least three or more different wavelengths oflight can be emitted. In one embodiment, each one of the LEDs can emit adifferent wavelength of light. In one embodiment, two or more of theLEDs can emit the same wavelength of light. The LED's can emitwavelengths that are in the human visible spectrum (for example, about380 to about 760 nm) including, but not limited to, wavelengths that arevisibly perceived as blue light, red light, green light, white light,orange light, yellow light, and other colors, as well as emitwavelengths that are not in the human visible spectrum including, butnot limited to, infrared wavelengths. Combinations of wavelengths in thevisible and non-visible spectrums may also be used. The light wavesemitted by the sensor 50 function in a manner similar to the RF wavesemitted by the sensor 5 in FIGS. 1-5 since both are electromagneticwaves. For example, referring to FIG. 8, light waves 60 emitted by theelement 54 penetrate into a target and reflect from an analyte in thetarget to form the returning light waves 62 which are detected, forexample the receive element 56 (or by an LED acting as a receiveelement).

With reference now to FIG. 13, one embodiment of a method 70 fordetecting at least one analyte in a target is depicted. The method inFIG. 13 can be practiced using any of the embodiments of sensor devicesdescribed herein including the sensor 5 and the sensor 50. In order todetect the analyte, the sensor 5, 50 is placed in relatively closeproximity to the target. Relatively close proximity means that thesensor 5, 50 can be close to but not in direct physical contact with thetarget, or alternatively the sensor 5, 50 can be placed in direct,intimate physical contact with the target. The spacing (if any) betweenthe sensor 5, 50 and the target can be dependent upon a number offactors, such as the power of the transmitted signal. Assuming thesensor 5, 50 is properly positioned relative to the target, at box 72the transmit signal is generated, for example by the transmit circuit15. The transmit signal is then provided to the transmit element (11 or54) which, at box 74, transmits the transmit signal toward and into thetarget. At box 76, a response resulting from the transmit signalcontacting the analyte(s) is then detected by the receive element (13,54, or 56). The receive circuit obtains the detected response from thereceive element and provides the detected response to the controller. Atbox 78, the detected response can then be analyzed to detect at leastone analyte. The analysis can be performed by the controller 19 and/orby the external device 25 and/or by the remote server 27.

Referring to FIG. 14, the analysis at box 78 in the method 70 can take anumber of forms. In one embodiment, at box 80, the analysis can simplydetect the presence of the analyte, i.e. is the analyte present in thetarget. Alternatively, at box 82, the analysis can determine the amountof the analyte that is present.

For example, in the case of the sensor being the sensor 5 and the signalbeing in the radio frequency range, the interaction between thetransmitted signal and the analyte may, in some cases, increase theintensity of the signal(s) that is detected by the receive antenna, andmay, in other cases, decrease the intensity of the signal(s) that isdetected by the receive antenna. For example, in one non-limitingembodiment, when analyzing the detected response, compounds in thetarget, including the analyte of interest that is being detected, canabsorb some of the transmit signal, with the absorption varying based onthe frequency of the transmit signal. The response signal detected bythe receive antenna may include drops in intensity at frequencies wherecompounds in the target, such as the analyte, absorb the transmitsignal. The frequencies of absorption are particular to differentanalytes. The response signal(s) detected by the receive antenna can beanalyzed at frequencies that are associated with the analyte of interestto detect the analyte based on drops in the signal intensitycorresponding to absorption by the analyte based on whether such dropsin signal intensity are observed at frequencies that correspond to theabsorption by the analyte of interest. A similar technique can beemployed with respect to increases in the intensity of the signal(s)caused by the analyte.

Detection of the presence of the analyte can be achieved, for example,by identifying a change in the signal intensity detected by the receiveantenna at a known frequency associated with the analyte. The change maybe a decrease in the signal intensity or an increase in the signalintensity depending upon how the transmit signal interacts with theanalyte. The known frequency associated with the analyte can beestablished, for example, through testing of solutions known to containthe analyte. Determination of the amount of the analyte can be achieved,for example, by identifying a magnitude of the change in the signal atthe known frequency, for example using a function where the inputvariable is the magnitude of the change in signal and the outputvariable is an amount of the analyte. The determination of the amount ofthe analyte can further be used to determine a concentration, forexample based on a known mass or volume of the target. In an embodiment,presence of the analyte and determination of the amount of analyte mayboth be determined, for example by first identifying the change in thedetected signal to detect the presence of the analyte, and thenprocessing the detected signal(s) to identify the magnitude of thechange to determine the amount.

In operation of either one of the sensors 5, 50 of FIGS. 1-12, one ormore frequency sweeps or scan routines can implemented. The frequencysweeps can be implemented at a number of discrete frequencies (rfrequency targets) over a range of frequencies. An example of afrequency sweep in a non-invasive analyte sensor using frequencies inthe radio/microwave frequency range is described in WO 2019/217461, theentire contents of which are incorporated herein by reference. In thecase of the sensor 50, a frequency sweep can be implemented with thesensor 50 at a number of discrete electromagnetic frequencies in thevisible wavelength range over a range of electromagnetic frequenciesbased on the different wavelengths of the LEDs. A response spectra isdetected by the receive element 56 or by the element 54 functioning as aphotodetector with the response spectra being correlated to a particularanalyte and analyte concentration.

In another embodiment, a non-invasive sensor can include aspects of bothof the sensors 5, 50. For example, a sensor can include both two or moreantennas as described herein as well as two or more of the LEDsdescribed herein. The antennas and the LEDs can be used together todetect an analyte. In another embodiment, the antennas can be used toperform a primary detection while the LEDs can confirm the primarydetection by the antennas. In another embodiment, the LEDs can be usedto perform a primary detection while the antennas can be used to confirmthe primary detection by the LEDs. In another embodiment, the antennas(or the LEDs) can be used to calibrate the sensor while the LEDs (or theantennas) can perform the sensing.

Referring now to FIGS. 15 and 16, systems and methods involving the useof the analyte sensors, for example similar to those described herein,to predict an actual or possible abnormal or normal condition, such asan abnormal medical condition, of a target are described. For sake ofconvenience, the systems and methods will be described as using theanalyte sensors 5, 50 described herein with respect to FIGS. 1-12. Inanother embodiment, the systems and methods can use the analyte sensorsdisclosed in U.S. Pat. No. 10,548,503, U.S. Patent ApplicationPublication 2019/0008422, or U.S. Patent Application Publication2020/0187791, each of which is incorporated herein by reference in itsentirety. Combinations of the features of the sensors 5, 50 describedherein and disclosed in U.S. Pat. No. 10,548,503, U.S. PatentApplication Publication 2019/0008422, or U.S. Patent ApplicationPublication 2020/0187791 can be used.

Referring initially to FIG. 15, a predictive medical analytics system200 according to one embodiment is illustrated. A similar system can beimplemented with other targets. The system 200 includes a receivingdevice 202 that is configured to receive analyte data directly orindirectly from one or more of the analyte sensors 5, 50. Each sensor 5,50 is interfaceable with a corresponding subject 204, for example ahuman or animal, for detecting at least one analyte in the subject 204.For example, the sensor 5, 50 may be worn by the subject 204, forexample worn around the subjects wrist, or the sensor 5, 50 may beincorporated into a device, such as a tabletop device or a hand-helddevice for detecting the analyte(s) in the subject 204. The sensor(s)204 conducts a plurality of analyte sensing routines to sense at leastone analyte in the subject 204, where the at least one analyte is anindicator of an abnormal medical pathology of the subject 204.

The analyte can be any analyte that is an indicator of an abnormalmedical pathology due to the presence of the analyte and/or due to theconcentration of the analyte. Many analytes as indicators of abnormalmedical pathologies are possible, too numerous to mention. For example,the analyte can be glucose where glucose concentration levels (eitherhigh (i.e. hyperglycemia) or low (i.e. hypoglycemia)) over a period oftime ae a well-known indicator of pre-diabetes or diabetes.

In another example, the analyte can be c-reactive proteins where highlevels of c-reactive proteins are an indicator of diabetes, thromboticevents including myocardial infarction, and some cancers such as lungcancer and breast cancer. See Mankowski et al., “Association ofC-Reactive Protein And Other Markers Of Inflammation With Risk OfComplications In Diabetic Subjects”, The Journal Of The InternationalFederation Of Clinical Chemistry And Laboratory Medicine, March 2006;Allin et al., “Elevated C-reactive protein in the diagnosis, prognosis,and cause of cancer”, Crit Rev Clin Lab Sci, July-August 2011.

In another example, the analyte can be ketones where high levels ofketones are an indicator of hyperglycemia and diabetes. See Mahendran etal., Association of Ketone Body Levels With Hyperglycemia and Type 2Diabetes in 9,398 Finnish Men”, Diabetes, Vol. 62, October 2013.

In another example, the analyte can be white blood cells where highlevels of white blood cells are an indicator of alcoholic livercirrhosis. See Alcoholic Liver Cirrhosis,https://www.healthline.com/health/alcoholic-liver-cirrhosis#symptoms,September 2018.

In another example, the analyte can be luteinizing hormone (LH) wheretoo much or too little LH can be an indicator of abnormal medicalpathology including infertility, menstrual difficulties in women, lowsex drive in men, and early or delayed puberty in children. SeeLuteinizing Hormone (LH) Levels Test,https://medlineplus.gov/lab-tests/luteinizing-hormone-lh-levels-test/#:˜:text=This%20test%20measures%20the%20level,helps%20control%20the%20menstrual%20cycle.

As shown in FIG. 15, the analyte sensor 5, 50 may be in wireless orwired communication with an intermediate device 206 which in turn is inwireless or wired communication with the receiving device 202, wherebythe receiving device 202 indirectly receives the analyte data from thesensor 5, 50. The intermediate device 206 can be any device that caninterface with the analyte sensor 5, 50 and the receiving device 202including, but not limited to, a mobile device such as a mobile phone, atablet computer, a laptop computer, or the like. The intermediate device206 may also be a personal computer. The intermediate device 206 mayalso be a specially designed device that is created specifically tointerface with the analyte sensor 5, 50 and the receiving device 202.The intermediate device 206 may be provided with an app designed by theentity that controls the receiving device 202 that allows theintermediate device 206 to function with the analyte sensor 5, 50 andthe receiving device 202. The intermediate device 206 may be owned bythe subject 204, or owned by a parent if the subject 204 is a child, orowned by a care giver if the subject 204 is under care of a care giver.Alternatively or additionally, the receiving device 202 may be in directwired or wireless communication with the analyte sensor 204 whereby thereceiving device 202 directly receives the analyte data from the sensor5, 50.

As used herein, receiving analyte data includes receiving the analytereadings from the analyte sensor 5, 50 whereby the analyte sensor 5, 50and/or the intermediate device 206 processes the signals detected by thereceive element of the sensor 5, 50 during a scan routine to determinethe presence and/or concentration of the analyte, with the processedanalyte data (i.e. the analyte presence and/or concentration readings)being sent to the receiving device 202. Therefore, the detected signalsmay be processed entirely by the analyte sensor 5, 50, the detectedsignals may be entirely processed by the intermediate device 206, or thedetected signals may be partially processed by the analyte sensor 5, 50and partially by the intermediate device 206. Receiving analyte data asused herein also includes receiving raw analyte readings from theanalyte sensor 5, 50 and/or the intermediate device 206 whereby the rawsignals detected by the receive element of the sensor 5, 50 are sent tothe receive device 202 and the receive device 202 processes the rawsignals to determine the presence and/or concentration of the analyte.Therefore, the detected signals may be processed entirely by thereceiving device 202, or the receiving device 202 may finish processingthe detected signals which have been partially processed by the analytesensor 5, 50 and/or the intermediate device 206. In another embodiment,the receive element 202 can receive both the processed analyte data andthe raw analyte data, with the receive element 202 processing the rawdata to determine the presence and/or concentration of the analyte forcomparison to the received processed analyte data.

The analyte data is collected by the sensor 5, 50 over a period of timethat is sufficient to indicate an actual or possible abnormal medicalpathology or condition of the subject 204. The time period over whichthe analyte data is collected may vary based on a number of factorsincluding, but not limited to, the subject 204, the analyte beingdetected, temporal factors (for example time of day, the day(s) of theweek, month or year), and other factors. The time period over which theanalyte data is collected can be measured in minutes, hours, days,months or even years. In one embodiment, the time period can be selectedto minimize or avoid collecting analyte data encompassing natural ornon-abnormal variations in the analyte of the subject 204 that may occurand that may not indicate an actual or possible abnormal medicalpathology of the subject 204. In another embodiment, to err on the sideof medical caution, the time period that is selected may includecollecting analyte data that encompasses natural or normal variations inthe analyte of the subject 204 that may occur whether or not all of thecollected analyte data indicates an actual or possible abnormal medicalpathology. For example, the plurality of analyte sensing routines can beconducted over a period of time of at least twenty four hours, 5 days, 1week, 1 month, 3 months, 6 months, 9 months, 1 year, and may others. Instill another embodiment, instead of collecting analyte data over aperiod of time, a single analyte reading can be used to predict anactual or possible abnormal medical pathology.

The scan routines conducted by the analyte sensor 5, 50 to obtain theanalyte data can occur continuously over the time period, or at regularor irregular intervals over the time period. The scan routines can beconducted automatically under control of a control system. In anotherembodiment, the scan routines can be manually triggered by the subject204. In still another embodiment, the scan routines can be conductedautomatically with the subject 204 also able to trigger one or moremanual scan routines upon demand.

The analyte data can be transmitted to and received by the receivingdevice 202 in multiple transmissions. For example, the analyte datacollected by the analyte sensor 5, 50 can be transmitted to thereceiving device 202 during or after each sensing routine over thesensing period. In another embodiment, the analyte data can betransmitted to and received by the receiving device 202 in a singletransmission. For example, the sensor 5, 50 or the intermediate device206 can store the analyte data from each scan routine and at the end ofthe sensing period, all of the analyte data from all of the scanroutines can be transmitted to the receiving device 202.

In an embodiment, a second sensor 208 can be interfaceable with thesubject 204 to detect second data of the subject 204 which istransmitted to the receiving device 202. The second sensor 208 can be asecond analyte sensor 5, 50 that can detect the same or differentanalyte as the sensor 5, 50, or the second sensor 208 can be a sensorthat detects another variable of the subject 204 such as, but notlimited to, heart rate, blood pressure, oxygen level, temperature,hydration, and others. The data from the second sensor 208 can be usedtogether with the analyte data from the sensor 5, 50 to predict theabnormal medical pathology of the subject 204.

The receiving device 202 includes one or more processors 210, one ormore non-transitory machine/computer-readable storage mediums (i.e.storage device(s)) 212, and one or more data storage 214. The receivingdevice 202 may be a server or other computer hardware. The receivingdevice 202 may also be implemented in a cloud computing environment.

The processor(s) 210 can have any construction that is suitable forprocessing the analyte data received by the receiving device 202. Theprocessor(s) 210 can be a microprocessor, microcontroller, embeddedprocessor, a digital signal processor, or any other type of logiccircuitry. The processor(s) 210 can be single core or multi-core.

The data storage 214 stores the analyte data received by the receivingdevice 202 and also stores the results of the data analysis performed bythe receiving device 202. The data storage 214 may also store an analytedatabase that is established from analyte readings obtained from thesubjects 204 over a period of time. The data storage 214 can be any formof longterm data storage. The data storage 214 may be implemented bycloud storage, or by data storage at a single location.

The at least one storage device 212 comprises program instructions thatare executable by the one or more processors 210 to configure thereceiving device 202 to be able to receive the analyte data, to transmitdata and/or commands to the analyte sensor 5, 50 and/or to theintermediate device 206, and optionally to communicate with one or morehealth care providers 216. The health care provider 216 can be thehealth care provider for the subject 204, for example a nurse, a doctoror other health care provider. The program instructions of the at leastone storage device 212 can further control other functions of thereceiving device 202 including general operation of the receiving device202, including internal and external communications, and interactionsbetween the various elements of the receiving device 202, and the like.

The at least one storage device 212 can further comprise programinstructions that are executable by the one or more processors 210 tofunction as a data analyzer 218 that analyzes the analyte data receivedfrom the sensor 5, 50 and/or from the intermediate device 206. The dataanalyzer 218 functions to analyze the received analyte data to determinethe presence of the analyte(s) and/or the concentration of theanalyte(s) in the manner described above.

The at least one storage device 212 can further comprise programinstructions that are executable by the one or more processors 210 tofunction as a medical pathology predictor 220 that uses the results ofthe analysis of the analyte data to predict an abnormal medicalcondition of the subject 204. For example, the medical pathologypredictor 220 can use the analyte data to detect trends in the analytesuggesting an actual or possible abnormal medical condition. Forexample, the mere presence of an analyte can indicate a possible oractual abnormal medical condition. In another example, a detectedanalyte level over a certain threshold, or below a certain threshold,for a period of time can be suggestive of an actual or possible abnormalmedical condition. In another example, significant changes in theanalyte level can be suggestive of an actual or possible abnormalmedical condition.

The receiving device 202 can generate an electronic report based on theresults of the analysis of the received analyte data. The report caninclude the results of the analysis, including a positive or normalanalysis (i.e. no abnormal medical pathology exists), or including apredicted abnormal medical pathology. In the case of a predictedabnormal medical pathology, the report may also include guidance to thesubject 204 on how to rectify the abnormal medical pathology, orguidance to seek medical attention to confirm and address the abnormalmedical pathology, or other guidance. The receiving device 202 mayinclude a display that displays the report, or the receiving device 202may transmit the electronic report to a location remote from thereceiving device 202. For example, the electronic report may betransmitted to the intermediate device 206 and/or to the analyte sensor5, 50 for display. The electronic report may be transmitted to thehealth care provider(s) 216 who in turn may provide the report to thesubject 204 or otherwise report the results to the subject 204.

In one embodiment, all of the elements of the system 200, including theanalyte sensor 5, 50, the intermediate device 206 and the receivingdevice 202 may be provided from and controlled by a single entity. Orthe entity may provide and control the analyte sensor 5, 50 and thereceiving device 202, and provide an app for downloading by the subject204 onto the intermediate device 206, for example a mobile phone ortablet owned by the subject 204, that configures the intermediate deviceto function with the analyte sensor 5, 50 and the intermediate device202. Or the entity may provide and control the receiving device 202, andprovide an app(s) for downloading by the subject 204 onto theintermediate device 206, for example a mobile phone or tablet owned bythe subject 204 and for downloading onto the analyte sensor 5, 50, forexample in the form of a smartwatch-like device owned by the subject204, that configures the intermediate device 206 and the analyte sensor5, 50 to function with the intermediate device 202.

A method 230 using the predictive medical analytics system 200 of FIG.15 is illustrated in FIG. 16. The method 230 includes, at step 232,obtaining analyte data from a plurality of targets (such as the targets204 in FIG. 15). The analyte data is obtained over a period of time, forexample at least 24 hours, from each target as described herein usingthe analyte sensors described herein. For example, the analyte data canbe sent to the receiving device 202 from the intermediate devices 206which receive the analyte data from the analyte sensors 5, 50. Theanalyte data can be sent to the receiving device 202 in multipletransmissions or in a single transmission. In addition, the analyte datacan be raw, unprocessed analyte data, or the analyte data can beprocessed data that has been processed by the intermediate device 206and/or by the analyte sensor 5, 50.

At step 234, the analyte database is established based on the analytedata that has been obtained from the targets. The analyte data in theanalyte database provides information on one or more analytes in theanalyte data. For example, in the case of analyte data from humantargets, the analyte data can indicate the presence and concentration ofan analyte such as glucose as previously described herein. The use ofanalyte data from multiple targets over a prolonged period of time helpsincrease the confidence that the obtained data is accurate and reducesthe impact of random variations in analyte levels in the targets.

Once the analyte database is established, at step 236 new or additionalanalyte data can be obtained from a target using one of the analytesensors described herein. The new analyte data is obtained from thetarget over a period of time, for example 24 hours or more. The targetcan be one of the targets used to establish the analyte database, or thetarget can be a new target that is different from the targets used toestablish the analyte database. In step 238, the new analyte data canoptionally be added to the analyte database to update the analytedatabase.

In step 240, the new analyte data is analyzed based on the analytedatabase. For example, the new analyte data can be analyzed, for exampleusing the medical pathology predictor 220 of FIG. 15, by comparing thenew analyte data to the analyte data in the analyte database todetermine the presence (or absence) of one or more analytes and/ordetermine a concentration of the one or more analytes using the analytedatabase. At step 242, an actual or possible condition of the target canthen be predicted based on the analysis of the new analyte data. Forexample, if the analysis reveals the presence of a particular analyte inthe new analyte data, or reveals a particular concentration of aparticular analyte, that can be an indicator of an abnormal (or normal)condition, such as an abnormal medical pathology of a human target.

FIG. 17 illustrates another example of a method 250 of using thepredictive medical analytics system 200 of FIG. 15. In this example, ananalyte database that is specific to a single individual is established.The method 250 includes, at step 252, obtaining analyte data from asingle target (such as one of the targets 204 in FIG. 15). The analytedata is obtained over a period of time, for example at least 24 hours,from the target as described herein using one or more of the analytesensors described herein. For example, the analyte data can be sent tothe receiving device 202 from the intermediate devices 206 which receivethe analyte data from the analyte sensor 5, 50. The analyte data can besent to the receiving device 202 in multiple transmissions or in asingle transmission. In addition, the analyte data can be raw,unprocessed analyte data, or the analyte data can be processed data thathas been processed by the intermediate device 206 and/or by the analytesensor 5, 50.

At step 254, the analyte database is established based on the analytedata that has been obtained from the single target. The analyte data inthe analyte database provides information on one or more analytes in theanalyte data. For example, in the case of analyte data from a humantarget, the analyte data can indicate the presence and concentration ofan analyte such as glucose as previously described herein. The use ofanalyte data from the single target over a prolonged period of timehelps increase the confidence that the obtained data is accurate andreduces the impact of random variations in analyte levels in the target.

Once the analyte database is established, at step 256 new or additionalanalyte data can be obtained from the target using one of the analytesensors described herein. The new analyte data is obtained from thetarget over a period of time, for example 24 hours or more. In step 258,the new analyte data can optionally be added to the analyte database toupdate the analyte database.

In step 260, the new analyte data is analyzed based on the analytedatabase. For example, the new analyte data can be analyzed, for exampleusing the medical pathology predictor 220 of FIG. 15, by comparing thenew analyte data to the analyte data in the analyte database todetermine the presence (or absence) of one or more analytes and/ordetermine a concentration of the one or more analytes using the analytedatabase and/or determine a change in the analyte. At step 262, anactual or possible condition of the target can then be predicted basedon the analysis of the new analyte data. For example, if the analysisreveals the presence of a particular analyte in the new analyte data, orreveals a particular concentration of a particular analyte, or reveals asignificant change in analyte, that can be an indicator of an abnormal(or normal) condition, such as an abnormal medical pathology of a humantarget.

In FIGS. 16 and 17, any one or more of the establishment of the analytedatabases, updating the analyte databases, analysis of the new analytedata, and predicting a condition of the target can be performed usingartificial intelligence techniques, such as using machine learningtechniques. For example, artificial intelligence software can be trainedto recognize different signals, that are obtained by the analyte sensorsdescribed herein, that correspond to different analytes at differentfrequencies. The artificial intelligence software can also be trained tocorrelate the recognized signals and the corresponding analyte(s) to oneor more corresponding determinations, such as an abnormal medicalpathology associated with the corresponding analyte(s).

The terminology used in this specification is intended to describeparticular embodiments and is not intended to be limiting. The terms“a,” “an,” and “the” include the plural forms as well, unless clearlyindicated otherwise. The terms “comprises” and/or “comprising,” whenused in this specification, specify the presence of the stated features,integers, steps, operations, elements, and/or components, but do notpreclude the presence or addition of one or more other features,integers, steps, operations, elements, and/or components.

The examples disclosed in this application are to be considered in allrespects as illustrative and not limitative. The scope of the inventionis indicated by the appended claims rather than by the foregoingdescription; and all changes which come within the meaning and range ofequivalency of the claims are intended to be embraced therein.

The invention claimed is:
 1. An analytics system, comprising: areceiving device that includes one or more processors and at least onestorage device; the at least one storage device comprising instructions,which when executed by the one or more processors, configure thereceiving device to: establish an analyte database that is based onanalyte data that is obtained from interstitial fluid of similar targetsby in vitro non-invasive analyte sensors that conduct a plurality ofanalyte sensing routines on the similar targets to obtain the analytedata from the interstitial fluid of the similar targets over a period oftime, the analyte data containing information on at least one analyte inthe interstitial fluid of the similar targets, and to receive theanalyte data in a single transmission from each one of the in vitronon-invasive analyte sensors resulting from the plurality of the analytesensing routines conducted by each one of the in vitro non-invasiveanalyte sensors, and each in vitro non-invasive analyte sensor includes:an antenna array having at least three antennas disposed side-by-side toone another, each one of the at least three antennas comprising anelongated strip of conductive material with a longitudinal axis, eachone of the at least three antennas has longitudinal ends, and thelongitudinal ends of the at least three antennas differ in geometricalshape from one another, at least one of the at least three antennas iscontrolled to operate as a transmit antenna and at least one of the atleast three antennas is controlled to operate as a receive antenna, andfor each analyte sensing routine of the plurality of analyte sensingroutines the transmit antenna transmits an electromagnetic transmitsignal that includes at least one frequency in a range of from 10 kHz to100 GHz into the interstitial fluid of the corresponding similar targetand the receive antenna detects a response resulting from transmissionof the electromagnetic transmit signal by the transmit antenna into theinterstitial fluid of the corresponding similar target; a transmitcircuit that is electrically connectable to the transmit antenna, thetransmit circuit is configured to generate the electromagnetic transmitsignal to be transmitted by the transmit antenna; and a receive circuitthat is electrically connectable to the receive antenna, the receivecircuit is configured to receive the response detected by the receiveantenna.
 2. The analytics system of claim 1, further comprising the invitro non-invasive analyte sensors, and the in vitro non-invasiveanalyte sensors are in direct and/or indirect communication with thereceiving device.
 3. The analytics system of claim 1, further comprisingintermediate devices that are in communication with the in vitronon-invasive analyte sensors and with the receiving device.
 4. Theanalytics system of claim 1, wherein the analyte data in the analytedatabase is raw unprocessed data obtained by the in vitro non-invasiveanalyte sensors, and wherein the instructions, when executed by the oneor more processors, further configure the receiving device to: analyzethe raw unprocessed data using the one or more processors to generateanalyzed data and store the analyzed data.
 5. The analytics system ofclaim 1, wherein the analyte data in the analyte database is rawunprocessed data obtained by the in vitro non-invasive analyte sensors,and wherein the instructions, when executed by the one or moreprocessors, further configure the receiving device to: analyze the rawunprocessed data to determine the presence of the at least one analytein the interstitial fluid and/or a concentration of the at least oneanalyte in the interstitial fluid.